RT Journal Article
SR Electronic
T1 Distant regulatory effects of genetic variation in multiple human tissues
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 074419
DO 10.1101/074419
A1 Brian Jo
A1 Yuan He
A1 Benjamin J. Strober
A1 Princy Parsana
A1 François Aguet
A1 Andrew A. Brown
A1 Stephane E. Castel
A1 Eric R. Gamazon
A1 Ariel Gewirtz
A1 Genna Gliner
A1 Buhm Han
A1 Amy Z. He
A1 Eun Yong Kang
A1 Ian C. McDowell
A1 Xiao Li
A1 Pejman Mohammadi
A1 Christine B. Peterson
A1 Gerald Quon
A1 Ashis Saha
A1 Ayellet V. Segrè
A1 Jae Hoon Sul
A1 Timothy J. Sullivan
A1 Kristin G. Ardlie
A1 Christopher D. Brown
A1 Donald F. Conrad
A1 Nancy J. Cox
A1 Emmanouil T. Dermitzakis
A1 Eleazar Eskin
A1 Manolis Kellis
A1 Tuuli Lappalainen
A1 Chiara Sabatti
A1 GTEx Consortium
A1 Barbara E. Engelhardt
A1 Alexis Battle
YR 2016
UL http://biorxiv.org/content/early/2016/09/09/074419.abstract
AB Understanding the genetics of gene regulation provides information on the cellular mechanisms through which genetic variation influences complex traits. Expression quantitative trait loci, or eQTLs, are enriched for polymorphisms that have been found to be associated with disease risk. While most analyses of human data has focused on regulation of expression by nearby variants (cis-eQTLs), distal or trans-eQTLs may have broader effects on the transcriptome and important phenotypic consequences, necessitating a comprehensive study of the effects of genetic variants on distal gene transcription levels. In this work, we identify trans-eQTLs in the Genotype Tissue Expression (GTEx) project data1, consisting of 449 individuals with RNA-sequencing data across 44 tissue types. We find 81 genes with a trans-eQTL in at least one tissue, and we demonstrate that trans-eQTLs are more likely than cis-eQTLs to have effects specific to a single tissue. We evaluate the genomic and functional properties of trans-eQTL variants, identifying strong enrichment in enhancer elements and Piwi-interacting RNA clusters. Finally, we describe three tissue-specific regulatory loci underlying relevant disease associations: 9q22 in thyroid that has a role in thyroid cancer, 5q31 in skeletal muscle, and a previously reported master regulator near KLF14 in adipose. These analyses provide a comprehensive characterization of trans-eQTLs across human tissues, which contribute to an improved understanding of the tissue-specific cellular mechanisms of regulatory genetic variation.